Inhibition of an in vitro CD4+ T cell alloresponse using altered peptide ligands

C Daniel, A Grakoui, PM Allen - The Journal of Immunology, 1998 - journals.aai.org
C Daniel, A Grakoui, PM Allen
The Journal of Immunology, 1998journals.aai.org
In this study, we explore the potential of altered peptide ligands (APLs) to modulate the
alloresponse of CD4+ T cells using elements of the murine hemoglobin (Hb) Ag model. We
first demonstrated that the T cell 2.102, specific for the Hb (64-76)/IE k complex, was
alloreactive against splenocytes of the H-2 p haplotype. Using Ab-blocking and transfection
experiments, we further showed that this alloreactivity was restricted to the class II molecule
IE p. We tested a panel of APLs previously shown to antagonize the Hb response of 2.102 …
Abstract
In this study, we explore the potential of altered peptide ligands (APLs) to modulate the alloresponse of CD4+ T cells using elements of the murine hemoglobin (Hb) Ag model. We first demonstrated that the T cell 2.102, specific for the Hb (64-76)/IE k complex, was alloreactive against splenocytes of the H-2 p haplotype. Using Ab-blocking and transfection experiments, we further showed that this alloreactivity was restricted to the class II molecule IE p. We tested a panel of APLs previously shown to antagonize the Hb response of 2.102 and found that these peptides could also effectively inhibit the alloresponse to IE p. Importantly, these peptides were able to antagonize the alloresponse of naive T cells derived from mice transgenic for the 2.102 TCR, as well as Th1 and Th2 cell lines. The antagonism required the presence of both IE p and IE k on the same APC. Our study demonstrates the effectiveness of APLs to antagonize the primary alloresponse of specific T cells and provides a basis for the development of immunotherapeutics for use in transplantation and immune-mediated diseases.
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